The Grand Opportunity provided by funding of this application will allow CARRA to rapidly transform the culture of pediatric rheumatology toward universal participation in research. This proposal is the first step in a major paradigm shift leading to global acceptance of evidence-based protocol-driven care as the optimal approach to treatment of pediatric rheumatic diseases by families, patients, and health care providers. Through the creation of sophisticated informatics infrastructure, provision of comprehensive site support and the engagement of families, patients, and communities, CARRA will provide the opportunity for affected children at every CARRA site to participate in high quality clinical and translational research. If CARRA could approach the level of research participation for children with rheumatic disease that the pediatric oncology research network (Children's Oncology Group, COG) has achieved for pediatric cancer, the health outcomes for all children with rheumatic disease would dramatically improve. To catapult the field of pediatric rheumatology research to the level of performance necessary to realize dramatic improvements in the outcomes and quality of life for all children with rheumatic disease, we propose four main strategies. 1) Investment in a CARRA-wide informatics platform with capabilities for capture, storage, visualization, and secure HIPAA-compliant sharing of validated disease metrics and relevant subject demographics, utilizing centralized Electronic Data Capture (EDC) during routine clinic visits and ontology-based data storage using a distributed database structure based on the NIH-supported i2b2 (Informatics Integrating Biology and the Bedside) framework. This will enable efficient, observational, disease-related data capture across CARRA sites for the major pediatric rheumatic diseases, (juvenile arthritis, systemic lupus, dermatomyositis, scleroderma, vasculitis, and pain syndromes) and support standardization of treatment protocols, clinical trials, observational disease registries, and comparative effectiveness research, forming the foundation for CARRA studies in the next decade. A platform of this scope also has the capacity to integrate clinical and translational research data and to facilitate future biomarker discovery and development as well as promote fundamental investigation into basic pathogenic mechanisms of rheumatic disease leading to improved treatments and possible cures. This transformative Grand Opportunity is not possible through any other funding mechanism. There will be significant return on this infrastructure investment as CARRA achieves greater success competing for future grant funding and developing public-private partnerships. 2) Provision of centralized, comprehensive site support to US CARRA sites through education, mentoring and funding. These approaches will enable full participation in the observational disease registry and maximize widespread participation in clinical/translational research. A coordinator network will be created and outreach to new sites will occur to insure the maximum number of children have access to participation in studies. 3) Development of a translational research laboratory network providing comprehensive translational study expert consultation mechanisms to facilitate biomarker discovery and development, as well as fundamental investigation into basic pathogenic mechanisms of rheumatic disease. Biospecimens will be stored in a state-of-the-art biorepository which can provide the level of security and sample integrity required, with ability to integrate with the CARRA distributed database. 4) Engagement of families and volunteer health advocacy organizations (e.g Arthritis Foundation, Friends of CARRA) through formation of an Advisory Board to assist in developing scientific priorities, understanding community barriers to clinical research participation, and facilitating local awareness of the burden of pediatric rheumatic disease and the advantages of clinical research participation. CARRA has the organization, and now potentially, the opportunity to change the culture of pediatric rheumatology from phenomologically- based treatment to true evidence- based treatment that will improve the lives of children with debilitating and disabling chronic rheumatic diseases. If successful, CARRA's exponential progress will serve as a model to be emulated by other emerging clinical research networks in rare diseases of adults and children.